Details

Autor(en) / Beteiligte

• Zhao, Wei
• Liu, Jia-Xin
• Guo, Fang
• Liu, Xin-Guang

Titel

Yeast MED2 is involved in the endoplasmic reticulum stress response and modulation of the replicative lifespan

Ist Teil von

• Mechanisms of ageing and development, 2020-12, Vol.192, p.111381-111381, Article 111381

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •MED2-deficient cells are sensitive to TM.•MED2 deficiency shortens the RLS.•MED2 overexpression increases ER stress resistance.•MED2 overexpression extends the RLS. Saccharomyces cerevisiae MED2/YDL005C is a subunit of the mediator complex (Mediator), which is responsible for tightly controlling the transcription of protein-coding genes by mediating the interaction of RNA polymerase II with gene-specific transcription factors. Although a high-throughput analysis in yeast showed that the MED2 protein exhibits altered cellular localization under hypoxic stress, no specific function of MED2 has been described to date. In this study, we first provided evidence that MED2 is involved in the endoplasmic reticulum (ER) stress response and modulation of the replicative life span. We showed that deletion of MED2 leads to sensitivity to the ER stress inducer tunicamycin (TM) as well as a shortened replicative lifespan (RLS), accompanied by increased intracellular ROS levels and hyperpolarization of mitochondria. On the other hand, overexpression of MED2 in wild-type (WT) yeast enhanced TM resistance and extended the RLS. In addition, the IRE1-HAC1 pathway was essential for the TM resistance of MED2-overexpressing cells. Moreover, we showed that MED2 deficiency enhances ER unfolded protein response (UPR) activity compared to that in WT cells. Collectively, these results suggest the novel role of MED2 as a regulator in maintaining ER homeostasis and longevity.